The University of Washington, Group Health Cooperative Alzheimer's Disease patient Registry (ADPR) is a model incident case registry for dementia and Alzheimer~s disease developed in 1986 in response to a National Institute of Aging request for proposals. This application is a competing continuation of the ADPR. The application proposes to continue follow-up of cases enrolled between January 1987 and may 1996, during which approximately 1,000 patients were enrolled. These cases have been and will continue to be part of ongoing studies of diagnostic markers, natural history and have served as sources of cases for other investigators at the University of Washington and throughout the country. During the last funding cycle, we established a cohort of 2,58 persons over age 65 from the Group Health enrollment. Based on biennial follow-up examinations, we are detecting all incident cases of Alzheimer~s disease and related dementias from this cohort. This application proposes to continue our follow-up and maintenance of this cohort. Our goal is to estimate age-group specific incident rates of Alzheimer~s disease and related dementias and to test environmental and genetic risk factors which have been previously identified in case-control studies. In addition, the methods of the cohort study have been standardized to companion cross-cultural studies of Japanese-Americans in Honolulu and Seattle, and Japanese in Hiroshima. Since these studies have similar design and data collection protocols, we propose to compare our results wit the results from these affiliated cross-cultural studies, comparing incidence rates, distribution of dementia subtypes, and distribution of risk factors in different sites. The cohort study design affords the opportunity to reduce bias in measurement of exposure and allows us to obtain truly incident dementia cases. The parallel cross- cultural studies offer a unique opportunity to take advantage of the natural variation in environmental exposures that occurs with population migration. Migration studies have traditionally been helpful in determining whether there are modifiable risk factors for prevention of important chronic diseases.